tbuckley/cabot-search huggingface dataset:
Efficacy of camrelizumab and apatinib combination therapy versus apatinib only in treatment of advanced hepatocellular carcinoma: A meta-analysis.
Authors: Sarya Swed, Karam R Motawea, Yossef Hassan AbdelQadir, Mohamed Gamal, Amro A El-Sakka, Omneya A Kandil, Basel Abdelazeem, Muhammad Abdelaziz, Engy A Wahsh
Journal: Journal of Clinical Oncology (2022)

e16147 Background: Recent studies have assessed the efficacy of some therapeutics in advanced hepatocellular carcinoma. Our aim is to perform a meta-analysis to compare the efficacy of Camrelizumab and Apatinib combination therapy versus Apatinib only in treatment of advanced hepatocellular carcinoma. Methods: We searched PubMed, WOS, Embase and Scopus databases. Inclusion criteria were clinical trials and cohort studies that evaluated the efficacy of Camrelizumab and Apatinib combination therapy or Apatinib only in treatment of advanced hepatocellular carcinoma. We excluded case reports, conference abstracts, editorials and animal studies. CMA software (version 3) was used to perform the meta-analysis. Continuous outcomes were presented as (mean and SD) and dichotomous outcomes as event ratio(ER), with 95% confidence interval (CI). Results: After complete screening, 12 studies were finally included in our study. 4 studies for combination of Camerlizumab and Apatinib while 8 studies investigated the role of Apatinib in patients with advanced hepatocellular carcinoma. The total number of patients included in the study is 844; 172 in combination group and 672 in Apatinib group. By indirect comparison, combination therapy is associated with a relatively better pooled survival rate (ER = 0.532, 95% CI [0.446, 0.615]) compared to Apatinib only therapy (ER = 0.262, 95% CI [0.218, 0.313]). Combination therapy was also associated with higher pooled rates of disease control (ER = 0.755, 95% CI [0.683, 0.815]) compared with Apatinib only (ER = 0.683, 95% CI [0.644, 0.720]). While the Combination therapy was associated with lower pooled rate of stable disease (ER = 0.13, 95% CI [0.339, 0.491]) than Apatinib (ER = 0.531, 95% CI [0.492, 0.570]). The overall survival time was significantly higher in combination therapy (Mean = 14.375, 95% CI [14.101, 14.649]) compared to the pooled mean survival time from Apatinib only therapy (Mean = 10.390, 95% CI [9.925, 10.855]). Conclusions: This study showed that Camrelizumab and Apatinib combination therapy is associated with increased survival rate, disease control and overall survival time in advanced hepatocellular carcinoma patients compared with Apatinib only. It revealed also that combination therapy is associated with lower stable disease than Apatinib only. Further multicenter clinical trials are needed to support our results.
Ramifications and healthcare costs of Clostridioides difficile infections in hospitalized patients with solid tumors.
Authors: Zahid Tarar, Pak Ho Au, Kelechi Nwabara, Diana Franco, Peter Egwom, Nanuli Gvazava, Mohammad Saleh, Ghulam Ghous
Journal: Journal of Clinical Oncology (2022)

e18801 Background: Clostridioides difficile infection (CDI) is notorious for its perilous effect on frail patients, but its assault is even more so threatening on cancer patients as they are more prone to CDI due to damage to intestinal mucosa by chemotherapy agents and weak immune system, hence higher risk of getting affected from hospital-acquired infections. Here we analyze National inpatient sample database (NIS) of hospitalized patients with solid tumors to find out aftermath of CDI in this particular patient population. Methods: We used NIS database from year 2019 and recruited all patients admitted with C. diff colitis with underline solid tumors with or without metastatic disease. We used international classification of disease,10 th revision (ICD-10) codes to identify these patients. Our outcomes of interest were all cause inpatient mortality, acute kidney injury (AKI), sepsis, ICU admission, pressor use and hospital resource utilization including mean length of stay (LOS) and mean total charges. Using STATA 17, we performed the multivariate regression analysis. Results: A total of 15,161 (1.41%) hospitalizations due to principal diagnosis of C. diff Colitis were recorded in solid tumor patients in year 2019. Patients with history of solid tumors who were admitted with C. diff colitis had higher adjusted odds of all-cause in-hospital mortality (AOR 1.23, 95% CI1.08-1.41, P 0.002) compared to patients without underline solid tumor. These patients also had higher odds of sepsis (AOR 2.22, 95% CI 1.89-2.59, P &lt; 0.001), AKI (AOR 1.91, 95% CI 1.73-2.10, P &lt; 0.001), ICU admission (AOR 1.66, 95% CI 1.39-1.97, P &lt; 0.001) and pressors use (AOR 1.82, 95% CI 1.38-2.40, P &lt; 0.001). Patients with underline solid tumors who developed C. diff colitis had increased mean LOS (AOR 3.88, 95% CI 3.41-4.34, P &lt; 0.001). These patients also incurred more hospital charges (Co-efficient 33836$, 95% CI 25907$-41766$, p &lt; 0.001). [Table]. Conclusions: Patients with solid tumors admitted with CDI have an increased risk of sepsis, AKI, ICU admission and in-hospital mortality. They also have a significantly longer duration of hospital stay; hence higher cost of care. There is a dire need for awareness regarding strict contact precautions, hand hygiene, effective environmental cleaning, minimizing antibiotics use/adherence to antibiotic stewardship programs, using prophylactic vancomycin where indicated, avoidance of unnecessary hospital visits utilizing telehealth, etc. and aggressive management of CDI in patients admitted to hospital with solid tumors.[Table: see text]
Treatment patterns and prognosis in inoperable stage III NSCLC after concurrent chemoradiotherapy with or without immune checkpoint inhibition: Historical overview.
Authors: Benedikt Flörsch, Julian Taugner, Lukas Käsmann, Saskia Kenndoff, Julian Guggenberger, Amanda Tufman, Niels Reinmuth, Thomas Duell, Claus Belka, Chukwuka Eze, Farkhad Manapov
Journal: Journal of Clinical Oncology (2022)

e20578 Background: To investigate the impact of treatment patterns in inoperable stage III NSCLC following concurrent chemoradiotherapy with or without immune checkpoint inhibition (cCRT±ICI). Methods: Patients were stratified by treatment year and divided into three subgroups: A (2011–2014), B (2015–2017) and C (2018–2020). Patient- and treatment-related characteristics regarding to PFS and OS were analyzed. Survival parameters were calculated from the last day of thoracic radiotherapy (TRT). Results: 136 consecutive enrolled patients were included. Median follow-up (FU) was 35.7 months; median age was 66.9 years. All patients completed TRT to a total dose ≥60.0 Gy; Median radiotherapy planning target volume (PTV) was 700 cc (range: 172.5–2293.2). Thirty-six (26%) patients received ICI. Median PFS in subgroups A, B and C was 8.0, 8.2 and 26.3 months (p = 0.007). Median OS was 19.9 months, 23.4 months and not reached in subgroups A, B and C (p &lt; 0.05). In subgroup C, median PFS was 14.2 vs. 26.3 months in patients treated with and without ICI. On multivariate analysis for the entire cohort, PTV &gt; 700cc was a negative prognosticator of PFS (HR: 1.522; p = 0.042) and OS (HR: 2.671; p = 0.001); ICI was a predictor of improved PFS (HR: 0.571; p = 0.071) and longer OS (HR: 0.401; p = 0.062). In the Non-ICI cohort, multivariate analyses revealed PTV &gt; 700cc (HR: 1.630; p = 0.047) and SUVmax &gt; 13.75 (HR: 1.859; p = 0.012) were predictors of reduced PFS; PTV &gt; 700cc (HR: 1.958; p = 0.017), SUVmax &gt; 13.75 (HR: 2.405; p = 0.002) and total lung V20 &gt; 30 (HR: 3.357; p &lt; 0.05) were predictors of longer OS. Conclusions: Regardless of ICI, patients receiving multimodal therapy after 2018 demonstrated improved survival compared to patients treated earlier. Both PTV &gt; 700cc and ICI were predictive for PFS and OS in the entire cohort.
A robust, trial-agnostic gene signature for response to tyrosine kinase inhibition in ccRRCC.
Authors: Sari Safaa Khaleel, Minwei Liu, Fengshen Kuo, Ritesh Kotecha, Chung-Han Lee, Martin H Voss, Robert J. Motzer, A. Ari Hakimi, Eduard Reznik
Journal: Journal of Clinical Oncology (2022)

4558 Background: Combination systemic therapies (ST) including immunotherapy (IO) and Tyrosine Kinase Inhibitors (TKI) have become the standard of care for management of metastatic clear cell carcinoma (ccRCC). Several expression (GE) signatures have been reported to predict TKI response with the aim of identifying the optimal ST regimen (IO/IO or IO/TKI) per patient. However, these gene signatures were developed and evaluated using data from individual trials with clinically distinct patient cohorts, fundamentally impeding their general application to diverse and heterogeneous patient populations. We therefore sought to identify genes consistently and directly associated with progression-free survival (PFS) with TKI ST across several trials. Methods: We applied a stratified, weighted concordance model to identify genes consistently demonstrating statistically significant association with PFS in the sunitinib TKI arm in four large randomized controlled trials (RCTs) of ST in ST-naïve ccRCC patients: COMPARZ (Motzer et al, 2013), Checkmate 214 (Motzer et al, 2018), IMmotion 151 (Rini et al, 2019), and Javelin 101 (Motzer et al, 2019). Concordant genes with Benjamini-Hochberg adjusted p-value (pAdj) ≤ 0.01 were selected. Of these, genes significantly associated with PFS on Cox proportional hazard regression (pAdj ≤ 0.05) in at least 3 of the 4 datasets were selected. Ontologic process and pathway enrichment analyses (OPPEA) against several ontologic databases were peformed using Metascape (Zhou et al, 2019). Results: We identified 2,794 statistically significant genes demonstrating concordant association with PFS across all 4 datasets (1087 patients); 71 genes were significantly associated with PFS on univariate post-hoc analysis in ≥3 of the datasets. OPPEA of these results identified significant enrichment in genes associated with cell cycle, cell division, and VEGFA-VEGFR2 pathways (Table 1). Although 5 genes in our set overlapped with published angiogenesis GES, the majority of these genes constitute entirely novel transcriptomic correlates of response to sunitinib. Conclusions: We developed a robust meta-gene signature consisting of genes directly and consistently associated with TKI response using data from several clinical trials. This gene signature is readily applicable to heterogeneous patient populations treated with anti-VEGF therapies. [Table: see text]
Factors associated with acute kidney injury among patients with cancer treated with immune checkpoint inhibitor therapy: A population-based study.
Authors: Phillip S. Blanchette, Lucie Richard, Salimah Shariff, Jacques Raphael, Craig Earle, Amit Garg, Abhijat Kitchlu
Journal: Journal of Clinical Oncology (2022)

2584 Background: Cancer immune checkpoint inhibitor (ICI) therapy may be associated with kidney immune-related adverse events (IRAEs) and other causes of acute kidney injury (AKI). In clinical trials, the frequency of AKI events was uncommon, however, further real-world study is warranted. Methods: We evaluated the proportion of AKI events among patients with advanced cancer (bladder, head and neck, lung, kidney and malignant melanoma) treated with ICI therapy in Ontario, Canada from 2012 - 2018. AKI was defined by a rise in the concentration of serum creatinine as per Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A multivariable regression model was used to identify predictors of AKI while accounting for the competing risk of death. Results: A total of 4,380 patients received ICI therapy. In follow-up, 1,283 (29%) had recorded AKI event (any stage AKI) and 289 (7%) had a severe AKI event (≥ stage 2). Median time to AKI was 6 months (Interquartile Range 2-16 months) and ≤ 1 % of patients received dialysis therapy. Within 30 days of any observed AKI event, 853 (58%) discontinued ICI therapy, 372 (29%) were hospitalized and 266 (21%) died. Mortality was significantly higher among patients who experiencing a severe AKI event (≥ stage 2) as compared to patients with a less severe AKI event (stage 1) or no observed AKI event. Among patients alive at 30 days following an AKI event, 14% received an outpatient corticosteroid or immunosuppressive therapy prescription, 7% had a visit with a nephrologist. Characteristics associated with a higher risk of AKI included female sex, bladder or kidney cancer (reference malignant melanoma), history of hypertension or diabetes, higher Charlson comorbidity score, a baseline estimated glomerular filtration rate less than 30 mL/min/1.73 m 2 , or outpatient prescription for either a proton pump inhibitor or non-steroidal anti-inflammatory drug. Among patients with an AKI event and treatment discontinuation, re-challenge of ICI therapy was infrequent (16%) with a significant risk of a recurrent AKI event (57%). Conclusions: In a population-based study among patients with cancer receiving ICI therapy, the rate of AKI was common (29%) but severe AKI was less frequent (7%). Rates of ICI discontinuation, hospitalization and death are substantial following an AKI event. Kidney function should be monitored carefully among patients undergoing ICI therapy who have common risk factors for developing renal disease. Nephrology consultation may be optimized among patients who develop a severe AKI event, especially among individuals who are considered for ICI therapy re-challenge.
A phase 1, first-in-human, drug dose-escalation study of RM-1995 photoimmunotherapy, as monotherapy or combined with pembrolizumab, in patients with advanced cutaneous squamous cell carcinoma or with head and neck squamous cell carcinoma.
Authors: David M. Cognetti, Joseph M. Curry, Rostislav KuklÃk, Ann M. Gillenwater
Journal: Journal of Clinical Oncology (2022)

TPS6103 Background: RM-1995 comprises an antibody against CD25, conjugated with a light-activatable dye (IRDye 700DX), which can subsequently be activated by illumination with 690 nm non-thermal red light for precise, targeted cell killing. Administration of the antibody-dye conjugate followed by local illumination results in target cell membrane disruption, while limiting damage to surrounding tissue. CD25 (lL-2Rα) is highly expressed by regulatory T cells (Tregs), thereby providing an opportunity to specifically target intratumoral Tregs for depletion via photoimmunotherapy. Tregs are critical in promoting immune homeostasis; however, in the context of solid tumors, Treg-mediated suppression detrimentally constrains anticancer T-cell responses, and a low ratio of CD8+ T cells:Tregs in the tumor is negatively correlated with clinical outcomes. Preclinical data suggest that RM-1995 photoimmunotherapy treatment alleviates local Treg-mediated restraint within the tumor microenvironment. Anticancer responses were further improved when combined with anti-PD-1 checkpoint inhibition. Methods: A phase 1 first-in-human dose-escalation study of RM-1995 photoimmunotherapy as monotherapy, or in combination with pembrolizumab, in patients with advanced cutaneous squamous cell carcinoma (cuSCC) and head and neck squamous cell carcinoma (HNSCC) is now enrolling (NCT05220748). The phase 1a portion will evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent RM-1995 photoimmunotherapy and determine the maximum tolerated dose or maximum administered dose of RM-1995 with a fixed light dose for tumor illumination. The phase 1b portion will include combination therapy with pembrolizumab. Enrolled patients will receive RM-1995 IV, followed 24±4 hours later by local tumor illumination. Pembrolizumab (200 mg) will be administered 5–7 days prior to RM-1995 infusion, then again 3 weeks later. Patients may be eligible to receive repeated photoimmunotherapy cycles for up to 12 months. Primary outcomes include safety and tolerability, and dose finding. The study will include cuSCC or HNSCC patients with locally advanced or locoregional disease with or without metastases that has recurred or progressed on or after platinum-based chemotherapy, and who are not eligible for further locoregional treatment. Other criteria include ECOG 0–2 and having ≥1 tumor accessible for illumination. Key exclusion criteria are: tumor sites located in sensitive or vital anatomic structures or invading a major blood vessel (unless treated to prevent hemorrhage); and other clinically significant or uncontrolled disease processes. An estimated 18 patients will be enrolled into each portion of the study. Clinical trial information: NCT05220748.
Efficacy and safety of the anti–PD-L1 monoclonal antibody socazolimab for recurrent or metastatic cervical cancer: Results from the phase I dose-escalation and expansion study.
Authors: Jusheng An, Li Guiling, Jie Tang, Benjamin Xiaoyi Li, Hui Hua Xiong, Hui Qiu, Lin Luo, Li Wang, Danbo Wang, Qi Zhou, Qin Xu, Hong Lin Song, Yun Yan Zhang, Hong Ping Zhang, Rachel Ng, Zewei Zhao, Xiang Rong Dai, Yu Jie Li, Yuanjue Sun, Lingying Wu
Journal: Journal of Clinical Oncology (2022)

5526 Background: The study (NCT03676959) is an open-label, phase I study investigating the safety and efficacy of the recombinant, fully human anti-programmed death-ligand 1 (PD-L1) monoclonal antibody socazolimab for recurrent or metastatic cervical cancer. Methods: Patients received socazolimab every 2 weeks until disease progression. The study was divided into a dose-escalation phase and a dose-expansion phase. Safety and tolerability were primary endpoints of the dose-escalation phase. Primary endpoints of the dose-expansion phase were safety and overall response rate (ORR) of the 5mg/kg dose. Efficacy was assessed by a third-party independent review committee (IRC) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as the evaluation standard. Pharmacokinetics and pharmacodynamics were also studied. Results: One hundred four patients were enrolled. Twelve patients were included in the dose-escalation phase, with one complete and two partial responses in the 5mg/kg treatment group. Ninety-two patients (5mg/kg) were enrolled in the dose-expansion phase, with 54 patients (59.3%) expressing baseline PD-L1-positive tumors. ORR was 15.4% (95% CI, 8.7 to 24.5%). Median PFS was 4.44 months (95% CI, 2.37 to 5.75 months), and the median OS was 14.72 months (95% CI, 9.59 to NE months). ORRs for PD-L1-positive and PD-L1-negative patients were 16.7% and 17.9%, respectively. Treatment-related grade 3 to 4 adverse events occurred in 7.7% of patients. No treatment-related deaths had occurred. Conclusions: Our study demonstrates that socazolimab has remarkable safety and efficacy for the treatment of recurrent or metastatic cervical cancer and exhibits a safety profile similar to other anti–PD-1/PD-L1 monoclonal antibodies. Clinical trial information: NCT03676959. [Table: see text]
Prompt assessment of tumor load and treatment response in patients with lymphoma by a blood-based multiomics approach.
Authors: Xinhua Wang, Zhi-Ming Li, Yu Chang, Yinyin Chang, Fangyuan Chang, Dandan Zhu, Wei Wu, Shiyong Li, Mingzhi Zhang, Mao Mao
Journal: Journal of Clinical Oncology (2022)

e19547 Background: Lymphomas represent a diverse group of diseases that arise from a clonal proliferation of lymphocytes. Periodic imaging is the current standard of care for clinical evaluation of treatment response for lymphoma patients, but It bears obvious shortcomings. Therefore, more accurate method is needed to evaluate treatment effect of Lymphoma. Methods: We present a real-time blood-based treatment response monitoring assay SeekInClarity to assess tumor load and response to varied treatment protocols in patients with lymphoma. A novel multidimensional molecular tumor burden (MTB) model was utilized. Copy number aberrations (CNAs) and fragment size (FS) patterns across the genome from sWGS data and levels of 7 PTMs (AFP, CEA, CA153, CA125, CA199, CYFRA21-1, CA724) are exploited to establish the MTB model. Patients with lymphoma were radiological assessed at baseline and reassessed regularly after treatment. The patients also had 10 ml venous blood samples collected for SeekInClarity at baseline and every two treatment cycles. Results: At baseline, 64.5% (80/124) patients were tested positive by SeekInClarity, implying the high MTB. In particular, genome-wide or focal CNA patterns were observed in 45.2% patients, and FS profile abnormality was witnessed from 42.5% patients, indicating both features are fundamental and ubiquitous surrogates of tumor burden. Elevated level of PTMs was also reported from 23.4% patients. All patients received various combination therapies with chemotherapies or immunotherapies as the backbone, and evaluated efficacy by clinical imaging. MTB evaluations of patients who underwent the follow-up SeekinClarity were compared with clinical imaging results. For the 44 patients who had negative MTB at baseline, 33 of them were performed following SeekinClarity and kept negative after treatment, and their imaging evaluations all showed remarkably curative effect. Furthermore, in the 80 patients with positive MTB, 57 patients were performed subsequent SeekinClarity tests, and a concordance of 81.6% was achieved with clinical evaluation. In addition, there was an 18.8% discordance between imaging evaluation and SeekinClarity. For these who had clinical partial response but unchanged or higher MTB, more tests and clinical evaluations are needed to assure the true clinical outcomes. Conclusions: This proof-of-concept study demonstrated SeekInClarity, a non-invasive, multidimensional multi-omics blood-based assay, can promptly evaluate the treatment response of patients with lymphoma. By implementing this assay, the dynamic change of MTB can help physicians to make well-informed decisions on the upcoming therapeutic strategies for each patient in conjunction with imaging. This study is still ongoing, and more cases and more time points are included to demonstrate the clinical performance of the assay.